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Skeletal muscles are composed of hundreds of multinucleated muscle fibers (myofibers) whose myonuclei are regularly positioned all along the myofiber’s periphery except the few ones clustered underneath the neuromuscular junction (NMJ) at the synaptic zone. This precise myonuclei organization is altered in different types of muscle disease, including centronuclear myopathies (CNMs). However, the molecular machinery regulating myonuclei position and organization in mature myofibers remains largely unknown. Conversely, it is also unclear how peripheral myonuclei positioning is lost in the related muscle diseases. Here, we describe the microtubule-associated protein, MACF1, as an essential and evolutionary conserved regulator of myonuclei positioning and maintenance, in cultured mammalian myotubes, in Drosophila muscle, and in adult mammalian muscle using a conditional muscle-specific knockout mouse model. In vitro, we show that MACF1 controls microtubules dynamics and contributes to microtubule stabilization during myofiber’s maturation. In addition, we demonstrate that MACF1 regulates the microtubules density specifically around myonuclei, and, as a consequence, governs myonuclei motion. Our in vivo studies show that MACF1 deficiency is associated with alteration of extra-synaptic myonuclei positioning and microtubules network organization, both preceding NMJ fragmentation. Accordingly, MACF1 deficiency results in reduced muscle excitability and disorganized triads, leaving voltage-activated sarcoplasmic reticulum Ca2+ release and maximal muscle force unchanged. Finally, adult MACF1-KO mice present an improved resistance to fatigue correlated with a strong increase in mitochondria biogenesis.

The formation of cheese flavor mainly results from the production of volatile compounds by microorganisms. We investigated how fine-tuning cheese-making process parameters changed the cheese volatilome in a semi-hard cheese inoculated with

Telomere shortening follows a developmentally regulated process that leads to replicative senescence of dividing cells. However, whether telomere changes are involved in postmitotic cell function and aging remains elusive. In this study, we discovered that the level of the TRF2 protein, a key telomere‐capping protein, declines in human skeletal muscle over lifetime. In cultured human myotubes, TRF2 downregulation did not trigger telomere dysfunction, but suppressed expression of the mitochondrial Sirtuin 3 gene (SIRT3) leading to mitochondrial respiration dysfunction and increased levels of reactive oxygen species. Importantly, restoring the Sirt3 level in TRF2‐compromised myotubes fully rescued mitochondrial functions. Finally, targeted ablation of the Terf2 gene in mouse skeletal muscle leads to mitochondrial dysfunction and sirt3 downregulation similarly to those of TRF2‐compromised human myotubes. Altogether, these results reveal a TRF2‐SIRT3 axis controlling muscle mitochondrial function. We propose that this axis connects developmentally regulated telomere changes to muscle redox metabolism., The level of the TRF2 protein, a key telomere‐capping protein, declines in human skeletal muscle over lifetime. In cultured human myotubes and in mouse skeletal muscle, TRF2 downregulation did not trigger telomere dysfunction, but suppressed expression of the mitochondrial Sirtuin 3 gene (SIRT3) leading to mitochondrial respiration dysfunction and increased levels of reactive oxygen species. Altogether, our results reveal a TRF2‐SIRT3 axis controling muscle mitochondrial function.

In this article, Osseni et al. show that by controlling acetylation of microtubules at neuromuscular junctions, HDAC6 regulates the insertion and removal of acetylcholine receptors. Accordingly, these findings provide key novel insights into the mechanisms involved in the stability and structure of neuromuscular junctions., Microtubules (MTs) are known to be post-translationally modified at the neuromuscular junction (NMJ), hence increasing their stability. To date however, the function(s) of the dynamic MT network and its relative stability in the formation and maintenance of NMJs remain poorly described. Stabilization of the MT is dependent in part on its acetylation status, and HDAC6 is capable of reversing this post-translational modification. Here, we report that HDAC6 preferentially accumulates at NMJs and that it contributes to the organization and the stability of NMJs. Indeed, pharmacological inhibition of HDAC6 protects against MT disorganization and reduces the size of acetylcholine receptor (AChR) clusters. Moreover, the endogenous HDAC6 inhibitor paxillin interacts with HDAC6 in skeletal muscle cells, colocalizes with AChR aggregates, and regulates the formation of AChR. Our findings indicate that the focal insertion of AChRs into the postsynaptic membrane is regulated by stable MTs and highlight how an MT/HDAC6/paxillin axis participates in the regulation of AChR insertion and removal to control the structure of NMJs.

The main objective of the proposed work is to perform stator flux and torque high dynamics response related to specific railway requirements such as anti-slid re-adhesion control. Moreover, this type of application takes into account DC bus voltage and current limitations. In addition, systems controlled by pulse width modulation (PWM) line side converters, injects harmonic current into the feeding overhead line. Therefore, it is necessary to consider an additional harmonic constraint (harmonic shape) as an entire part of the global control system in order not to interfere with signaling systems. Consequently, the high dynamics control objectives must be considered together with the PWM constraint and voltage/current limitations, as a single control task. Real-time simulation as well as experimental results for a specific railway test bench will be presented to highlight the performances of such control algorithm.

Acetylcholine receptor (AChR) expression in innervated muscle is limited to the synaptic region. Neuron-induced electrical activity participates in this compartmentalization by promoting the repression of AChR expression in the extrasynaptic regions. Here, we show that the corepressor CtBP1 (C-terminal binding protein 1) is present on the myogenin promoter together with repressive histone marks. shRNA-mediated downregulation of CtBP1 expression is sufficient to derepress myogenin and AChR expression in innervated muscle. Upon denervation, CtBP1 is displaced from the myogenin promoter and relocates to the cytoplasm, while repressive histone marks are replaced by activating ones concomitantly to the activation of myogenin expression. We also observed that upon denervation the p21-activated kinase 1 (PAK1) expression is upregulated, suggesting that phosphorylation by PAK1 may be involved in the relocation of CtBP1. Indeed, preventing CtBP1 Ser158 phosphorylation induces CtBP1 accumulation in the nuclei and abrogates the activation of myogenin and AChR expression. Altogether, these findings reveal a molecular mechanism to account for the coordinated control of chromatin modifications and muscle gene expression by presynaptic neurons via a PAK1/CtBP1 pathway.

This paper proposes a new discrete‐time formulation of state‐space model for voltage source inverter (VSI) fed AC motors, introducing the free evolution of the motor state and characterized by both the simplification of torque and flux output equations and the definition of a predictive reference frame oriented on the rotor free evolution vector. The potential of the proposed model for high dynamics discrete‐time controller synthesis is illustrated through an application to SM‐PMSM.

Skeletal muscle atrophy is a severe condition of muscle mass loss. Muscle atrophy is caused by a down-regulation of protein synthesis and by an increase of protein breakdown due to the ubiquitin-proteasome system and autophagy activation. Up-regulation of specific genes, such as the muscle-specific E3 ubiquitin ligase MAFbx, by FoxO transcription factors is essential to initiate muscle protein ubiquitination and degradation during atrophy. HDAC6 is a particular HDAC, which is functionally related to the ubiquitin proteasome system via its ubiquitin binding domain. We show that HDAC6 is up-regulated during muscle atrophy. HDAC6 activation is dependent on the transcription factor FoxO3a, and the inactivation of HDAC6 in mice protects against muscle wasting. HDAC6 is able to interact with MAFbx, a key ubiquitin ligase involved in muscle atrophy. Our findings demonstrate the implication of HDAC6 in skeletal muscle wasting and identify HDAC6 as a new downstream target of FoxO3a in stress response. This work provides new insights in skeletal muscle atrophy development and opens interesting perspectives on HDAC6 as a valuable marker of muscle atrophy and a potential target for pharmacological treatments.

To compensate for the extremely low penetration efficiency of the original PDS/1000-He Bio Rad biolistic® device and the deleterious blast effect, design modifications have been made to the launching module. These modifications were evaluated on Bombyx mori embryos and fragile tissues, such as oocytes and imaginal wing disks. The original floppy macrocarrier was replaced by a rigid macrocarrier to avoid the effects of the helium blast. The efficiency of the gene gun bombardment was reinforced by the addition of a focusing nozzle. The reduced blast effect allowed us to carry out high-pressure shootings to small organs with improved penetration. This system allowed potentially all the internal embryonic tissues to be transfected with optimal survival rates. The new module was effective on tissues that are difficult to transfect, such as the epithelial wing disk that is covered by a peripodial membrane, and the ovarian follicle cells that lie under the ovariole cell membrane. The new macrocarrier allowed both an aqueous delivery of particles and an ethanolic dry delivery. No significant differences were noted between these two modes of delivery. The major improvement is the possibility of high pressure shooting correlated with appreciable penetration and a weak blast effect.

We have developed a rapid facile synthesis of 1-ferrocenyl-3-alkyl and 1,3-di(ferrocenylmethyl)imidazolium salts. The imidazolium salts are formed in excellent yields.

Ferrocenylimidazolium salts have been synthesised as novel anion receptors. 1 H NMR studies showed that these compounds bind Cl − , Br − , I − , NO 3 − and HSO 4 − anions strongly in CDCl 3 through C–H···X − hydrogen bonding.

Syntheses of dehydrorotenoid and benzoxanthone units from 2′-hydroxyacetophenone are described which feature a novel migration of spiro-substituted chroman-4-ones during their oxidative ring expansion. Conjugate reduction affords a trans B/C fused rotenoid and the related cis and trans fused tetrahydrobenzoxanthones.

A transgenesis programme has been developed for Impatiens balsamina that will allow elucidation of the roles played by individual genes in the flower reversion phenomenon shown by this model species. The lack of explants exhibiting adventitious shooting in I. balsamina hinders Agrobacterium-based transformation, but the multiple shoots that arise from cotyledonary nodes present a suitable target for biolistics. These tissues can be disrupted by the helium blast effect associated with conventional biolistic devices, so we have utilised modifications to the PDS 1000/He equipment originally developed for transformation of fragile insect tissues. By loading microcarriers on to a rigid, rather than flexible, macrocarrier, the blast effect is largely eliminated, and the use of a focussing nozzle allows the bombardment to be concentrated on the target tissues. This approach reduces waste of plasmid DNA and gold microcarriers and achieves transfection at lower, less disruptive helium pressures than would otherwise be necessary to efficiently penetrate below the shoot epidermis and generate heritable transgenic lines.

A transgenesis programme has been developed for Impatiens balsamina that will allow elucidation of the roles played by individual genes in the flower reversion phenomenon shown by this model species. The lack of explants exhibiting adventitious shooting in I. balsamina hinders Agrobacterium-based transformation, but the multiple shoots that arise from cotyledonary nodes present a suitable target for biolistics. These tissues can be disrupted by the helium blast effect associated with conventional biolistic devices, so we have utilised modifications to the PDS 1000/He equipment originally developed for transformation of fragile insect tissues. By loading microcarriers on to a rigid, rather than flexible, macrocarrier, the blast effect is largely eliminated, and the use of a focussing nozzle allows the bombardment to be concentrated on the target tissues. This approach reduces waste of plasmid DNA and gold microcarriers and achieves transfection at lower, less disruptive helium pressures than would otherwise be necessary to efficiently penetrate below the shoot epidermis and generate heritable transgenic lines.

So as to reduce size, volume, weight and increase efficiency of power supplies for electrical sequential loads, authors propose to analyze functioning and disfunctioning of two converter topologies: inverter + power sharing system; matrix converter. A system with two electrical machines is analyzed through simulations from the control point of view and the design point of view considering over-current conditions constraints. Theses preliminary results enhance the possibility to use matrix converters.

International audience; So as to reduce size, volume, weight and increase efficiency of power converters for sequentially electrical loads, authors propose to analyze electromechanical switches, semiconductor switches linked to PWM converter and matrix converters. Existing power switches are studied and specific components developed specially for such converter are explained. To finish, new semiconductor materials are highlighted to give future trends in power electronics converters.

The benzothienopyranols 3, readily available from the ketone 1, are transformed to the carbamates 5 on treatment with N,N-dimethylcarbamoyl chloride, subsequent thermal electrocyclisation provides access to dibenzothiophene derivatives 6 and 11–13.

We have developed a rapid facile synthesis of 1-ferrocenyl-3-alkyl and 1,3-di(ferrocenylmethyl)imidazolium salts. The imidazolium salts are formed in excellent yields.

In adult skeletal muscle, the nicotinic acetylcholine receptor (AChR) specifically accumulates at the neuromuscular junction, to allow neurotransmission. This clustering is paralleled by a compartmentalization of AChR genes expression to subsynaptic nuclei, which acquire a unique gene expression program and a specific morphology in response to neural cues. Our results demonstrate that neural agrin‐dependent reprogramming of myonuclei involves chromatin remodelling, histone hyperacetylation and histone hyperphosphorylation. Activation of AChR genes in subsynaptic nuclei is mediated by the transcription factor GABP. Here we demonstrate that upon activation, GABP recruits the histone acetyl transferase (HAT) p300 on the AChR e subunit promoter, whereas it rather recruits the histone deacetylase HDAC1 when the promoter is not activated. Moreover, the HAT activity of p300 is required in vivo for AChR expression. GABP therefore couples chromatin hyperacetylation and AChR activation by neural factors in subsynaptic nuclei.

Position control of a hybrid driven circuit breaker is presented. Hybrid drive is the association of an accurate servo controlled motor and a reliable spring operating mechanism. High accurate position control of the circuit breaker contacts is performed through high dynamic torque control of the motor. Both simulation and experimental results highlight excellent performances

Robust speed control of a low damped electromechanical system with backlash is studied, controlled load angular speed being not measured. The proposed control strategy combines a Luenberger observer (load angular speed and load torque disturbance estimations) and a robust CRONE controller. The observer provides estimation of the load angular speed and of the disturbance torque applied on the load. Through the computation of only three independent parameters (as many as a PID controller), the CRONE controller permits to ensure the robust speed control of the load in spite of plant parametric variations and speed observation errors. The proposed control strategy is applied to a four mass experimental test bench.

This paper proposes a high dynamics torque control for surface mounted permanent magnet synchronous motor (SM-PMSM), based on a discrete-time model. To satisfy our goal, the so-called "Discrete-Time Field Oriented Control (DTFOC)" is used. One of the most important difficulties is to deal with the voltage or/and current limitation constraints. Therefore, by taking into account a priori these constraints, the proposed controller results in an optimal torque dynamics over full speed operation range. Real-time simulation and experimental results are presented to highlight the performances of such control algorithm.

A photophysical study of the interaction between dihydrogen phosphate anions and a series of ruthenium polypyridyl complexes containing anion receptor 4,4'-bis[(2-methoxyethyl)carbamoyl]-2,2'-bipyridine (L1) is reported. The complexes investigated are of the type [Ru(L)[2](L1)]X[2] and [Ru(L1)[3]]X[2], where L is 2,2'-bipyridyl or 1,10-phenanthroline and X is chloride or PF[6]-. The emission properties of the compounds are studied as a function of the anion concentrations using emission lifetime and steady-state measurements. For the mixed ligand complexes the emission intensity and lifetime increases upon the addition of 2.5 molar equivalents of H[2]PO[4]-, further additions do not result in further increases. For [Ru(L1)[3]]X[2] the emission increases upon addition of the first 2.5 equivalents of dihydrogen phosphate, however, further increases lead to a decrease in both emission intensity and lifetime. The effect of the addition of trace amounts of water is also examined.

International audience; Transgenesis was recently achieved in Bombyx mori L., but it has proved difficult and time-consuming to screen the numerous progeny to identify the transgenic individuals. As the 3xP3-EGFP marker has been shown to be a suitable universal marker for transgenic insects (Nature 402 (1999) 370), we evaluated its use for embryonic-stage screening for B. mori L. germline transformation. Using the piggyBac-derived vector pBac[3xP3-EGFPaf], we were able to isolate four transgenic individuals from about 120,000 embryos (560 broods). The screening was straightforward due to EGFP production in the G1 embryonic stemmata, which was visible through the translucent egg chorion. EGFP was produced in the stemmata and central and peripheral nervous systems from the fifth day of embryonic development. It persisted at high levels in the stemmata throughout the larval stage, and was also present in the compound eyes and nervous tissues of the pupae and the compound eyes of the moths.

We investigated the effects of in vivo exposure to non-lethal concentrations of two chemicals commonly discharged into the aquatic environment, prochloraz and nonylphenol diethoxylate (NP2EO - Igepal(R) 210), on the development of spermatogenesis in trout. The in vitro effects on basal and insulin-like growth factor-1 (IGF-I) stimulated DNA synthesis by early germ cells were also studied. In vivo, rainbow trout were exposed for 2 or 3 weeks to waterborne prochloraz (21 and 175 nmol/l) and/or NP2EO (68-970 nmol/l) renewed continuously, or periodically. Only the highest concentrations of NP2EO (225-970 nmol/l) induced a significant increase in blood plasma vitellogenin in juvenile or maturing male trout. When prepubertal fish were exposed for 15 days to prochloraz, the spermatogenetic process was significantly inhibited as shown by the stage of gonadal development reached 3 weeks after exposure. This effect was, to a great extent, reversible within 9 weeks post-exposure. When fish in the initial stage of spermatogenesis were exposed for 21-27 days to 580 nmol/l NP2EO, a 20-40% reduction of the gonadosomatic index was observed 4.5 weeks post-exposure, and the spermatogenetic process was partly inhibited. In vitro, testicular cells obtained at different stages of spermatogenesis were cultured for 4.5 days in the presence or not of the tested molecules and with IGF-I or not. 3H-thymidine (3H-Tdr) incorporation was measured according to Loir (Mol. Reprod. Dev. 53 (1999) 424) and 125I-IGF-I specific binding was determined according to Le Gac et al. (Mol. Reprod. Dev. 44 (1996) 35). Irrespective of the spermatogenetic stage, basal 3H-Tdr incorporation was decreased by prochloraz concentrationsor =10 micromol/l. The presence of IGF-I (10-100 ng/ml) stimulated 3H-Tdr incorporation; this response to IGF-I began to decrease at 25-50 micromol/l prochloraz. In parallel, a dose-dependent increase of IGF-I specific binding was induced by prochloraz 1-100 micromol/l. Similarly, basal and IGF-I-stimulated 3H-Tdr incorporation was decreased by nonylphenol polyethoxylate (NpnEO; starting at 10 micromol/l), NP2EO and NP (30 micromol/l); a dose-dependent increase of IGF-I specific binding was also induced by NP and NPnEO. While 1-100 nmol/l 17beta-estradiol had no effect in our in vitro system, Triton(R) X-100 acted as NPnEO on 3H-Tdr incorporation. Beside their known endocrine disrupting effects on sex steroid production or action, these lipophilic molecules could act on germ cells by disrupting cell membrane receptivity to peptide hormones like growth factors.

The title compound, [Fe(C₅H₅)(C₁₉H₁₄ClN₂)], a model electroactive agent for anion sensor and malarial parasite studies, has Fe-C bond lengths in the range 2.020 (3)-2.0543 (18) Å. The Fe...Cg distances (Cg indicates a ring centroid) are essentially similar, with values of 1.6467 (10) and 1.6487 (11) Å for the substituted and unsubstituted cyclopentadienyl rings, respectively, with a linear Cg...Fe...Cg angle of 179.12 (7)°. The Fe-CCp-Csp³ angle is 128.43 (13)° and the Fe1-CCp-Csp³-NBz torsion angle 110.27 (17)° (Cp is cyclopentadienyl and Bz is benzimidazole). Weak C-H...Cl contacts form the only intermolecular interactions of significance.

This paper proposes a high dynamic digital control scheme for IGBT based VSC HVDC power transmission, i.e. VSC-HVDC system, based on equivalent continuous-time state-space models for the rectifier/inverter actuators, using a nonlinear approach. In this paper, both tracking and regulation problems are presented in order to perform a robust DC-bus voltage control. Results illustrate the good behaviour of the system variables in response to positive and negative active power steps.

This paper deals with the direct torque control of high voltage/high power induction motors fed by floating capacitor multilevel VSI actuators. The active control strategy for balancing the capacitor voltages is presented highlighting an optimal pattern. The efficiency of this approach is compared to the well-known passive method and it is illustrated by simulation. In the next section, a controlled cycle based algorithm is proposed as an attractive solution for high performance torque control, satisfying the constant switching frequency required by IGBT. Associated simulation results show the good behaviour of this algorithm.

Three methods of isolating primordial germ cells (PGCs) from gonads of 5-day-old chick embryos were compared. PGCs were then cultured in vitro in DMEM/F12 medium containing 10% fetal calf serum. BrdU incorporation showed that at least 10% of the PGC population were dividing, under our culture conditions, during the 2nd day of in vitro culture. During this culture period, PGCs were exposed to avian leukosis sarcoma virus-based retroviral vector pseudotyped with subgroup A envelope, carrying the LacZ reporter gene. X-Gal staining showed that PGCs were permissive to infection, with more than 50% of PGCs expressing the beta-Gal protein. These data represent the first demonstration that PGCs, isolated from gonads of 5-day-old chick embryos, are able to divide in vitro and that it is possible to introduce and express exogenous DNA in chick PGCs maintained in vitro.

The benzothienopyranols 3, readily available from the ketone 1, are transformed to the carbamates 5 on treatment with N,N-dimethylcarbamoyl chloride, subsequent thermal electrocyclisation provides access to dibenzothiophene derivatives 6 and 11–13.

A novel class of anion receptors with with C-H···X- hydrogen bonding is introduced and demonstrated for Cl-, Br-, NO3- and HSO4- recognition. Cyclic voltammetry revealed that novel ferrocenylimidazolium salts, syntheses of which are briefly described, selectively complex and electrochemically recognise guest anions. Futhermore, proton NMR spectroscopy indicated the formation of 1:2 stoichiometric complexes with Cl-, Br and I- and 1:1 stoichiometric complexes with NO3- and HSO4-.